Dysfunction of the endothelin (ET) system may contribute to the etiology and progression of pulmonary arterial hypertension (PAH), a rapidly progressing and fatal condition of the cardiopulmonary system. The loss of endothelial cell integrity, whether through genetic predisposition or environmental damage, and the accompanying reduction in nitric oxide and increase in ET production are all recognized parts of the disease process.1
Circulating levels of ET have been reported to correlate with disease severity in PAH.2 In addition, the pulmonary vascular endothelium produces excess ET in patients with PAH, particularly at the site of the most significant pathology,3 suggesting that local production of ET may contribute to disease development and progression.3
   
PULMONARY ARTERIAL HYPERTENSION (PAH)
    
 
Clinical Definition4,5
  
•  
Mean pulmonary arterial pressure >25
mm Hg at rest (>30 mm Hg with exercise)
  
•  
Normal pulmonary capillary wedge pressure (PCWP)
  
•  
Associated with arteriopathy and resultant
right ventricular strain
REFERENCES
1. 
Gaine S. Pulmonary hypertension. JAMA. 2000;284:3160-3168.
2. 
Braunwald E, Zipes DP, Libby P, eds. Heart Disease. 2 vols. 6th ed. Philadelphia, PA: WB Saunders Co; 2001:1912, 1919.
3. 
Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol. 1999;61:391–415.
4. 
Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328:1732–1739.
5. 
Gaine SP, Rubin LJ. Primary pulmonary hypertension. Lancet. 1998;352:719–725.
6. 
Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997;336:111–117.
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